Abstract
A better understanding of the central role of inflammation in the development of coronary
artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies
targeting the interleukin-1ß/interleukin-6 cytokine signaling pathway, involved in
both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As
an inexpensive pharmacologic agent with relatively few adverse effects that tend to
be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic
events has been the focus of multiple recent large-scale randomized controlled trials
involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions
(Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5
mg once daily) should be considered in patients with recent myocardial infarctions—within
30 days and, ideally, within 3 days—or with stable CAD to improve cardiovascular outcomes.
Colchicine should not be used in patients with severe renal or hepatic disease because
of the risk of severe toxicity. No serious adverse effect was associated with the
combined use of colchicine and high-intensity statin therapy in large trials. The
impact of colchicine in high-risk populations of patients with peripheral arterial
disease and in those with diabetes for the primary prevention of CAD remains to be
established.
Résumé
Une meilleure compréhension du rôle central de l'inflammation dans le développement
de la coronaropathie (CP) a été à l'origine de l'évaluation de stratégies thérapeutiques
ciblant la voie de signalisation des cytokines interleukine-1ß/interleukine-6, impliquée
à la fois dans l'athérogénèse chronique et dans le déclenchement de la rupture de
la plaque d'athérome. En tant qu'agent pharmacologique peu coûteux, dont les effets
indésirables sont relativement peu nombreux et généralement légers et tolérables,
le rôle de la colchicine dans la prévention secondaire des événements athérothrombotiques
a fait l'objet de plusieurs essais contrôlés randomisés à grande échelle menés récemment
auprès de patients atteints de CP stable (essais LoDoCo [Low-Dose Colchicine] et LoDoCo2), après un infarctus du myocarde récent (essais COLCOT [Colchicine Cardiovascular Outcome Trial], COPS [Colchicine in Patients With Acute Coronary Syndrome] et CLEAR SYNERGY [Colchicine and Spironolactone in Patients With Myocardial
Infarction/Synergy Stent Registry]) et pour des patients subissant une intervention
coronarienne percutanée (ICP) (essai COLCHICINE-PCI). Sur la base de ces données,
la colchicine à faible dose (0,5 mg une fois par jour) doit être envisagée chez les
patients ayant subi un infarctus du myocarde récent - dans les 30 jours et, idéalement,
dans les trois jours - ou présentant une CP stable afin d'améliorer le pronostic cardiovasculaire.
La colchicine ne doit pas être utilisée chez les patients présentant une affection
rénale ou hépatique sévère, en raison d'un risque de toxicité grave. Aucun effet indésirable
grave n'a été associé à l'utilisation combinée de la colchicine et d'un traitement
par statine de haute intensité dans les essais à grande échelle. L'impact de la colchicine
dans les populations à haut risque des patients atteints de maladie artérielle périphérique
et chez les diabétiques pour la prévention primaire de la CP reste à établir.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet. 2018; 392: 1736-1788
- Targeting cardiovascular inflammation: next steps in clinical translation.Eur Heart J. 2021; 42: 113-131
- Emerging anti-inflammatory therapies for atherosclerosis.Curr Pharm Des. 2013; 19: 5840-5849
- Inflammation, immunity, and infection in atherothrombosis: JACC Review Topic of the Week.J Am Coll Cardiol. 2018; 72: 2071-2081
- Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective.Eur Heart J. 2015; 36: 1163-1170
- Post-discharge bleeding and mortality following acute coronary syndromes with or without PCI.J Am Coll Cardiol. 2020; 76: 162-171
- A prospective natural-history study of coronary atherosclerosis.N Engl J Med. 2011; 364: 226-235
- A randomized trial of colchicine for acute pericarditis.N Engl J Med. 2013; 369: 1522-1528
- EULAR recommendations for the management of familial Mediterranean fever.Ann Rheum Dis. 2016; 75: 644
- 2020 American College of Rheumatology guideline for the management of gout.Arthritis Care Res. 2020; 72: 744-760
- Efficacy and safety of low-dose colchicine after myocardial infarction.N Engl J Med. 2019; 381: 2497-2505
- Anti-inflammatory treatment with colchicine in acute myocardial infarction.Circulation. 2015; 132: 1395-1403
- Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients.J Am Coll Cardiol. 2013; 61: 1679-1685
- Low-dose colchicine for secondary prevention of cardiovascular disease.J Am Coll Cardiol. 2013; 61: 404-410
- Colchicine in patients with chronic coronary disease.N Engl J Med. 2020; 383: 1838-1847
- Effects of acute colchicine administration prior to percutaneous coronary intervention.Circ Cardiovasc Interv. 2020; 13e008717
- Colchicine in patients with acute coronary syndrome.Circulation. 2020; 142: 1890-1900
- The low dose colchicine after myocardial infarction (LoDoCo-MI) study: a pilot randomized placebo controlled trial of colchicine following acute myocardial infarction.Am Heart J. 2019; 215: 62-69
- Colchicine acutely suppresses local cardiac production of inflammatory cytokines in patients with an acute coronary syndrome.J Am Heart Assoc. 2015; 4e002128
- Inflammation, atherosclerosis, and coronary artery disease.N Engl J Med. 2005; 352: 1685-1695
- The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study.Eur Heart J. 2015; 36: 377-384
- Low-dose methotrexate for the prevention of atherosclerotic events.N Engl J Med. 2018; 380: 752-762
- Antiinflammatory therapy with canakinumab for atherosclerotic disease.N Engl J Med. 2017; 377: 1119-1131
- Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils.J Clin Invest. 1995; 96: 994-1002
- The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation.Atherosclerosis. 2018; 269: 262-271
- Technical advance: inhibition of neutrophil chemotaxis by colchicine is modulated through viscoelastic properties of subcellular compartments.J Leukocyte Biol. 2013; 94: 1091-1096
- Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation.PLoS One. 2010; 5: e11765
- Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease.Am J Cardiol. 2007; 99: 805-807
- Colchicine therapy and plaque stabilization in patients with acute coronary syndrome: a CT coronary angiography study.JACC Cardiovasc Imaging. 2018; 11: 305-316
- Colchicine inhibits neutrophil extracellular trap formation in patients with acute coronary syndrome after percutaneous coronary intervention.J Am Heart Assoc. 2021; 10e018993
- Colchicine attenuates inflammation beyond the inflammasome in chronic coronary artery disease.Circulation. 2020; 142: 1996-1998
- Using absolute event rates to see what works in cardiovascular medicine.J Am Coll Cardiol. 2017; 70: 1376-1378
- Increase in interleukin-6 in the first hour after coronary stenting: an early marker of the inflammatory response.J Thromb Thrombolysis. 2003; 15: 25-31
- Inflammatory response to percutaneous coronary intervention in stable coronary artery disease.J Thromb Thrombolysis. 2011; 31: 92-98
- Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty.J Am Coll Cardiol. 1996; 28: 1127-1133
- Low-dose colchicine in patients treated with percutaneous coronary interventions for myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).Eur Heart J. 2020; : 41
- Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).Eur Heart J. 2020; 41: 4092-4099
- Cost-effectiveness of low-dose colchicine after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).Eur Heart J Qual Care Clin Outcomes. 2021; 7: 486-495
- Colchicine for secondary prevention of cardiovascular disease: a systematic review and meta-analysis of randomized controlled trials.Can J Cardiol. 2021; 37: 776-785
- Meta-analysis evaluating the utility of colchicine in secondary prevention of coronary artery disease.Am J Cardiol. 2021; 140: 33-38
- Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.Eur Heart J. 2021; 42: 2765-2775
- Colchicine for secondary cardiovascular prevention in coronary disease.Circulation. 2020; 142: 1901-1904
- Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials.Arthritis Res Ther. 2020; 22: 28
- Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis.Heart. 2016; 102: 590-596
- Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation: a randomized controlled study.J Am Coll Cardiol. 2012; 60: 1790-1796
- Anti-inflammatory treatment with colchicine in stable chronic heart failure: a prospective, randomized study.J Am Coll Cardiol HF. 2014; 2: 131-137
- Use of colchicine in pregnancy: a systematic review and meta-analysis.Rheumatology. 2018; 57: 382-387
- 2021 ESC guidelines on cardiovascular disease prevention in clinical practice: developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies with the special contribution of the European Association of Preventive Cardiology (EAPC).Eur Heart J. 2021; 42: 3227-3337
Article info
Publication history
Published online: August 18, 2021
Accepted:
August 16,
2021
Received:
June 29,
2021
Footnotes
See page 1843 for disclosure information.
Identification
Copyright
© 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
